It is known that various protein kinases exist in in vivo and are involved in the regulation of a variety of functions. Bruton's tyrosine kinase (BTK) is a protein kinase that belongs to the Tec family kinases, and is a non-receptor tyrosine kinase that plays an important role related to the control of, for example, proliferation, survival, differentiation and activation of B-cells in the downstream of the B cell receptor (BCR) signal (Non-Patent Document 1). An inhibitor capable of controlling the activity of BTK is considered to be useful as a therapeutic agent for diseases associated with abnormal hyperactivity of BTK signaling pathway (for example, cancer).
Regarding a compound having BTK inhibitory activity, PCI-32765 (Non-Patent Document 2) and the compounds described in Patent Documents 1 and 2 are known.
The compounds disclosed in Patent Documents 1 and 2 are also known to exhibit high inhibitory activity for EGFR (Epidermal Growth Factor Receptor) and JAK3 (Janus kinase 3) for example, in addition to BTK. However, since such a multikinase inhibitor suppresses, for example, cell proliferation by inhibiting various signaling pathways, there is a concern about a variety of side effects. For example, it is known that EGFR binds to its ligand, for example, the epidermal growth factor (EGF), and participates in the proliferation and survival (for example, inhibition of apoptosis) of various cells (Non-Patent Document 3). However, it is known that inhibitors targeting EGFR cause side effects such as skin disorders and gastrointestinal dysfunction in common, and it is widely supposed that these side effects may be related to the inhibition of the wild type EGFR signaling pathway (Non-Patent Document 4).
Thus, PCI-45292 is known as a compound, which has an inhibitory activity against BTK with a weak inhibitory activity against EGFR (Non-Patent Document 5).
As described above, from the viewpoint of reducing side effects, a highly selective BTK inhibitor, that has a high inhibitory activity against BTK with low inhibitory activities against other kinases such as EGFR, is desired.